The proposed investigations are directed toward the study of collagen loss during periodontal disease due to collagenase activity. Specifically, a number of agents and several cell types will be tested for their ability to induce active collagenase in cultured cells. Agents to be tested will include plaque extracts, mast cell and lymphocyte sonicates, gingival (normal and inflamed) extracts, Dilantin sodium, dexamethasone, thyroxine, parathormone, prostaglandins, and endotoxin. Cell types to be tested include T lymphocytes, B lymphocytes and mast cells. Cells to be cultured include fibroblasts (from gingiva removed from patients manifesting Dilantin hyperplasia, periodontitis and fibromatosis) and pulmonary macrophages. Experiments will be conducted to determine whether the appearance of active collagenase in cell cultures results from the induction of collagenase or the induction of procollagenase activating enzyme. The data will be used to evaluate mechanisms which regulate the levels of active collagenase in the periodontium.